A community-engaged approach to developing a mHealth HIV/STI and drug abuse preventative intervention for primary care: a qualitative study

BACKGROUND: Despite ongoing prevention efforts, HIV and other sexually transmitted infections (HIV/STIs) and drug use remain public health concerns. Urban adolescents, many of whom are underserved and racial minorities, are disproportionately affected. Recent changes in policy, including the Affordable Care Act, and advances in technology provide HIV/STI and drug abuse prevention scientists with unique opportunities to deliver mobile health (mHealth) preventive interventions in primary care. OBJECTIVES: The purpose of this community-engaged study was to develop an mHealth version of the Storytelling for Empowerment preventive intervention for primary care (hereinafter referred to as “S4E”). Methods: A total of 29 adolescents were recruited from a youth-centered primary care clinic in Southeast, Michigan, to participate in qualitative interviews. Participants were predominantly African American (n=19, 65.5%) and female (n=21, 72.4%) with a mean age of 16.23 (SD 2.09). The principles of community-based participatory research (CBPR), in conjunction with agile software development and the recommended core prevention principles of the National Institute on Drug Abuse (NIDA) were employed during S4E development. CBPR principles are aimed at improving the effectiveness of research by addressing locally relevant health problems, working with community strengths, and translating basic science into applied research. Complementing this approach, the NIDA prevention principles are derived from decades of drug abuse prevention research aimed at increasing the effectiveness and uptake of programs, through the development of culturally specific interventions and ensuring the structure, content, and delivery of the intervention fit the needs of the community. Data were analyzed using thematic analysis. RESULTS: A total of 5 themes emerged from the data: (1) acceptability of the mHealth app to adolescents in primary care, (2) inclusion of a risk assessment to improve clinician-adolescent HIV/STI and drug use communication, (3) incorporation of culturally specific HIV/STI and drug use content, (4) incorporation of interactive aspects in the app to engage youth, and (5) perspectives on the appearance of the app. CONCLUSIONS: There is a dearth of mHealth HIV/STI and drug abuse preventive interventions for primary care. Incorporating the principles of CBPR in conjunction with agile software development and NIDA-recommended core prevention principles may be helpful in developing culturally specific mHealth interventions. An important next step in this program of research is to examine the feasibility, acceptability, and efficacy of S4E on adolescent sexual risk and drug use behaviors, and HIV/STI testing. Implications for prevention research and primary care practice are discussed in the context of the Affordable Care Act and technological advances.http://mhealth.jmir.org/2015/4/e106/http://mhealth.jmir.org/2015/4/e106/Published versio

An epidemiological study of burglary offenders: trends and predictors of self-reported arrests for burglary in the United States, 2002-2013

Burglary is serious property crime with a relatively high incidence and has been shown to be variously associated with other forms of criminal behavior. Unfortunately, an epidemiological understanding of burglary and its correlates is largely missing from the literature. Using public-use data collected between 2002 and 2013 as part of the National Survey on Drug Use and Health (NSDUH), the current study compared those who self-reported burglary arrest in the prior 12 months with and without criminal history. The unadjusted prevalence estimates of self-reported burglary arrest were statistically different for those with a prior arrest history (4.7%) compared with those without an arrest history (0.02%) which is a 235-fold difference. Those with an arrest history were more likely to report lower educational attainment, to have lower income, to have moved more than 3 times in the past 5 years, and to use alcohol, tobacco, illicit drugs, and engage in binge drinking. Moreover, those with prior arrest histories were younger and more likely to be male. There is considerable heterogeneity among burglars with criminal history indicating substantially greater behavioral risk

Oxygen-rich dust production in IC 10

We report the detection of oxygen-rich circumstellar envelopes in stars of the nearby (700 kpc) starburst galaxy IC 10. The star formation history and the chemical environment of this galaxy makes it an ideal target to observe dust production by high-mass stars in a low-metallicity environment. The goal of this study is to identify oxygen-rich stars in IC 10 and to constrain their nature between asymptotic giant branch stars (AGBs), red supergiants (RSGs), and other infrared bright sources. We examine the mass-loss rate of the stars and compare to results obtained for the Magellanic Clouds. Our objectives are to (1) assess whether RSGs can be significant dust producers in IC 10, and (2), solve the discrepancy between the star formation history of IC 10 and the relatively low number of RSGs detected in the optical. We search for silicate dust in emission by using the spectral map observed with the Infrared Spectrograph on board the Spitzer Space Telescope. The optical (UBVRI) and infrared (JHK, Spitzer/IRAC and Spitzer/MIPS) photometry is used to assert the membership of the stars to IC 10 and disentangle between AGBs and RSGs. Radiative models are used to infer mass-loss rates and stellar luminosities. The luminosity and colors of at least 9 silicate emission sources are consistent with stars within IC 10. Furthermore, the photometry of 2 of these sources is consistent with RSGs. We derive dust mass-loss rates similar to the values found in the Magellanic Clouds. Accounting for the sample completeness, RSGs are not important contributors to the dust mass budget in IC 10.Comment: Accepted for publication in A&

HERUS: the far-IR/submm spectral energy distributions of local ULIRGs and photometric atlas

We present the Herschel-SPIRE photometric atlas for a complete flux limited sample of 43 local ultraluminous infrared galaxies (ULIRGs), selected at 60 μm by IRAS, as part of the HERschel ULIRG Survey (HERUS). Photometry observations were obtained using the SPIRE instrument at 250, 350, and 500 μm. We describe these observations, present the results, and combine the new observations with data from IRAS to examine the far-infrared spectral energy distributions (SEDs) of these sources. We fit the observed SEDs of HERUS objects with a simple parametrized modified blackbody model, where temperature and emissivity β are free parameters. We compare the fitted values to those of non-ULIRG local galaxies, and find, in agreement with earlier results, that HERUS ULIRGs have warmer dust (median temperature T = 37.9 ± 4.7 K compared to 21.3 ± 3.4 K) but a similar β distribution (median β = 1.7 compared to 1.8) to the Herschel reference sample (HRS, Cortese et al. 2014) galaxies. Dust masses are found to be in the range of 107.5–109 M⊙, significantly higher than that of HRS sources. We compare our results for local ULIRGs with higher redshift samples selected at 250 and 850 μm. These latter sources generally have cooler dust and/or redder 100-to-250  μm colours than our 60 μm-selected ULIRGs. We show that this difference may in part be the result of the sources being selected at different wavelengths rather than being a simple indication of rapid evolution in the properties of the population

The ALMA detection of CO rotational line emission in AGB stars in the Large Magellanic Cloud

Context. Low- and intermediate-mass stars lose most of their stellar mass at the end of their lives on the asymptotic giant branch (AGB). Determining gas and dust mass-loss rates (MLRs) is important in quantifying the contribution of evolved stars to the enrichment of the interstellar medium. Aims: This study attempts to spectrally resolve CO thermal line emission in a small sample of AGB stars in the Large Magellanic Cloud (LMC). Methods: The Atacama Large Millimeter Array was used to observe two OH/IR stars and four carbon stars in the LMC in the CO J = 2-1 line. Results: We present the first measurement of expansion velocities in extragalactic carbon stars. All four C stars are detected and wind expansion velocities and stellar velocities are directly measured. Mass-loss rates are derived from modelling the spectral energy distribution and Spitzer/IRS spectrum with the DUSTY code. The derived gas-to-dust ratios allow the predicted velocities to agree with the observed gas-to-dust ratios. The expansion velocities and MLRs are compared to a Galactic sample of well-studied relatively low MLRs stars supplemented with extreme C stars with properties that are more similar to the LMC targets. Gas MLRs derived from a simple formula are significantly smaller than those derived from dust modelling, indicating an order of magnitude underestimate of the estimated CO abundance, time-variable mass loss, or that the CO intensities in LMC stars are lower than predicted by the formula derived for Galactic objects. This could be related to a stronger interstellar radiation field in the LMC. Conclusions: Although the LMC sample is small and the comparison to Galactic stars is non-trivial because of uncertainties in their distances (hence luminosities), it appears that for C stars the wind expansion velocities in the LMC are lower than in the solar neighbourhood, while the MLRs appear to be similar. This is in agreement with dynamical dust-driven wind models

Analysis of blood and nasal epithelial transcriptomes to identify mechanisms associated with control of SARS-CoV-2 viral load in the upper respiratory tract

Objectives: The amount of SARS-CoV-2 detected in the upper respiratory tract (URT viral load) is a key driver of transmission of infection. Current evidence suggests that mechanisms constraining URT viral load are different from those controlling lower respiratory tract viral load and disease severity. Understanding such mechanisms may help to develop treatments and vaccine strategies to reduce transmission. Combining mathematical modelling of URT viral load dynamics with transcriptome analyses we aimed to identify mechanisms controlling URT viral load. Methods: COVID-19 patients were recruited in Spain during the first wave of the pandemic. RNA sequencing of peripheral blood and targeted NanoString nCounter transcriptome analysis of nasal epithelium were performed and gene expression analysed in relation to paired URT viral load samples collected within 15 days of symptom onset. Proportions of major immune cells in blood were estimated from transcriptional data using computational differential estimation. Weighted correlation network analysis (adjusted for cell proportions) and fixed transcriptional repertoire analysis were used to identify associations with URT viral load, quantified as standard deviations (z-scores) from an expected trajectory over time. Results Eighty-two subjects (50% female, median age 54 years (range 3–73)) with COVID-19 were recruited. Paired URT viral load samples were available for 16 blood transcriptome samples, and 17 respiratory epithelial transcriptome samples. Natural Killer (NK) cells were the only blood cell type significantly correlated with URT viral load z-scores (r = −0.62, P = 0.010). Twenty-four blood gene expression modules were significantly correlated with URT viral load z-score, the most significant being a module of genes connected around IFNA14 (Interferon Alpha-14) expression (r = −0.60, P = 1e-10). In fixed repertoire analysis, prostanoid-related gene expression was significantly associated with higher viral load. In nasal epithelium, only GNLY (granulysin) gene expression showed significant negative correlation with viral load. Conclusions: Correlations between the transcriptional host response and inter-individual variations in SARS-CoV-2 URT viral load, revealed many molecular mechanisms plausibly favouring or constraining viral replication. Existing evidence corroborates many of these mechanisms, including likely roles for NK cells, granulysin, prostanoids and interferon alpha-14. Inhibition of prostanoid production and administration of interferon alpha-14 may be attractive transmission-blocking interventions

Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children.

IMPORTANCE: Because clinical features do not reliably distinguish bacterial from viral infection, many children worldwide receive unnecessary antibiotic treatment, while bacterial infection is missed in others. OBJECTIVE: To identify a blood RNA expression signature that distinguishes bacterial from viral infection in febrile children. DESIGN, SETTING, AND PARTICIPANTS: Febrile children presenting to participating hospitals in the United Kingdom, Spain, the Netherlands, and the United States between 2009-2013 were prospectively recruited, comprising a discovery group and validation group. Each group was classified after microbiological investigation as having definite bacterial infection, definite viral infection, or indeterminate infection. RNA expression signatures distinguishing definite bacterial from viral infection were identified in the discovery group and diagnostic performance assessed in the validation group. Additional validation was undertaken in separate studies of children with meningococcal disease (n = 24) and inflammatory diseases (n = 48) and on published gene expression datasets. EXPOSURES: A 2-transcript RNA expression signature distinguishing bacterial infection from viral infection was evaluated against clinical and microbiological diagnosis. MAIN OUTCOMES AND MEASURES: Definite bacterial and viral infection was confirmed by culture or molecular detection of the pathogens. Performance of the RNA signature was evaluated in the definite bacterial and viral group and in the indeterminate infection group. RESULTS: The discovery group of 240 children (median age, 19 months; 62% male) included 52 with definite bacterial infection, of whom 36 (69%) required intensive care, and 92 with definite viral infection, of whom 32 (35%) required intensive care. Ninety-six children had indeterminate infection. Analysis of RNA expression data identified a 38-transcript signature distinguishing bacterial from viral infection. A smaller (2-transcript) signature (FAM89A and IFI44L) was identified by removing highly correlated transcripts. When this 2-transcript signature was implemented as a disease risk score in the validation group (130 children, with 23 definite bacterial, 28 definite viral, and 79 indeterminate infections; median age, 17 months; 57% male), all 23 patients with microbiologically confirmed definite bacterial infection were classified as bacterial (sensitivity, 100% [95% CI, 100%-100%]) and 27 of 28 patients with definite viral infection were classified as viral (specificity, 96.4% [95% CI, 89.3%-100%]). When applied to additional validation datasets from patients with meningococcal and inflammatory diseases, bacterial infection was identified with a sensitivity of 91.7% (95% CI, 79.2%-100%) and 90.0% (95% CI, 70.0%-100%), respectively, and with specificity of 96.0% (95% CI, 88.0%-100%) and 95.8% (95% CI, 89.6%-100%). Of the children in the indeterminate groups, 46.3% (63/136) were classified as having bacterial infection, although 94.9% (129/136) received antibiotic treatment. CONCLUSIONS AND RELEVANCE: This study provides preliminary data regarding test accuracy of a 2-transcript host RNA signature discriminating bacterial from viral infection in febrile children. Further studies are needed in diverse groups of patients to assess accuracy and clinical utility of this test in different clinical settings

Identification of Rigosertib for the Treatment of Recessive Dystrophic Epidermolysis Bullosa–Associated Squamous Cell Carcinoma

PURPOSE: Squamous cell carcinoma (SCC) of the skin is the leading cause of death in patients with the severe generalized form of the genetic disease recessive dystrophic epidermolysis bullosa (RDEB). Although emerging data are identifying why patients suffer this fatal complication, therapies for treatment of RDEB SCC are in urgent need. EXPERIMENTAL DESIGN: We previously identified polo-like kinase 1 (PLK1) as a therapeutic target in skin SCC, including RDEB SCC. Here, we undertake a screen of 6 compounds originally designated as PLK1 inhibitors, and detail the efficacy of the lead compound, the multipathway allosteric inhibitor ON-01910, for targeting RDEB SCC in vitro and in vivo. RESULTS: ON-01910 (or rigosertib) exhibited significant specificity for RDEB SCC: in culture rigosertib induced apoptosis in 10 of 10 RDEB SCC keratinocyte populations while only slowing the growth of normal primary skin cells at doses 2 orders of magnitude higher. Furthermore, rigosertib significantly inhibited the growth of two RDEB SCC in murine xenograft studies with no apparent toxicity. Mechanistically, rigosertib has been shown to inhibit multiple signaling pathways. Comparison of PLK1 siRNA with MEK inhibition, AKT inhibition, and the microtubule-disrupting agent vinblastine in RDEB SCC shows that only PLK1 reduction exhibits a similar sensitivity profile to rigosertib. CONCLUSIONS: These data support a “first in RDEB” phase II clinical trial of rigosertib to assess tumor targeting in patients with late stage, metastatic, and/or unresectable SCC